Dearomative Mislow–Braverman–Evans Rearrangement of Aryl Sulfoxides

The Mislow–Braverman–Evans rearrangement,
the reversible
[2,3]-sigmatropic rearrangement of allylic sulfoxides to allylic sulfenate
esters, finds widespread applications in organic synthesis and medicinal
chemistry. However, the products of this powerful strategy have primarily
been limited to derivatives of allylic alcohols. In contrast, access
to structurally similar benzylic alcohols has not yet been established.
Described herein is an unprecedented dearomative Mislow–Braverman–Evans
rearrangement of aryl sulfoxides to afford benzylic alcohols. A variety
of heteroaryl sulfoxides as well as α-naphthyl sulfoxides could
be tolerated, and a diverse range of primary, secondary, and tertiary
alcohols possessing either alkyl or aryl substituents can be prepared
by our protocol with broad functional group tolerance. A patented
bioactive molecule could be prepared using our protocol as the key
step with exclusive diastereoselectivity, highlighting its potential
utility in organic synthesis. Key to the success of the transformation
is the dearomative tautomerization to shift the reactive alkene to
the exocyclic position enabled by the reversible deprotonation of
the benzylic C–H bond, setting the stage for the subsequent
[2,3]-sigmatropic rearrangement. Density functional theory (DFT) calculations
reveal that protonation of the α-carbon of the sulfoxide is
the stereocontrolling step, generating the intermediate that undergoes
[2,3]-sigmatropic rearrangement. The full reaction profile is outlined,
showing the reversible nature of each step, which causes the observed
erosion of the enantiopurity.